This program-project application is for the renewal of a center grant to facilitate, expand and strengthen programs of research and research training at the Rose F. Kennedy Center. This Center was established as a major step in the realization of an organized, multidisciplinary research and research training program in mental retardation and related aspects of human development. The major organizational feature of this program is its successful emphasis on interdisciplinary and multidisciplinary investigations. Such collaborative efforts among Kennedy Center investigators with divergent scientific backgrounds have resulted in the development of several new projects which have as their central objective the definition of fundamental morphophysiological and neurobehavioral correlations associated with the genesis of mental retardation. Biochemical and morphologic studies are defining severe degenerative disorders associated with mental retardation. Cytogenic, biochemical genetics and development physiologic studies are also being made. The basic premise in this program is that the acquisition of information concerning the normal and abnormal development of progressively more complex hierarchies of organization and the application of this knowledge to human development constitutes an approach that is immediately relevant to the problems of the cause and management of mental retardation.